Medicine Marrow Pg No 825-834 (Acid-Base Regulation)
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Which of the following is NOT a contraindication for arterial blood gas analysis?

  • Abnormal Allen's test
  • Normal arterial pressure (correct)
  • Severe peripheral vascular artery disease
  • Local infection at puncture site
  • The radial artery is the only site recommended for arterial blood gas puncture.

    False

    What is the primary parameter measured in arterial blood gas analysis to assess acidity or alkalinity?

    pH

    The normal value for $PCO_2$ in arterial blood gas analysis is _____ mmHg.

    <p>40</p> Signup and view all the answers

    Match the following types of acid-base disorders with their definitions:

    <p>Metabolic acidosis = A decrease in blood pH due to excess acid or loss of bicarbonate Metabolic alkalosis = An increase in blood pH due to excessive bicarbonate or loss of acid Respiratory acidosis = An increase in carbon dioxide due to impaired gas exchange Respiratory alkalosis = A decrease in carbon dioxide due to hyperventilation</p> Signup and view all the answers

    Which hormone is primarily responsible for helping us sleep?

    <p>Melatonin</p> Signup and view all the answers

    Serotonin levels increase at night due to the decrease in light signals.

    <p>False</p> Signup and view all the answers

    What is the primary source of serotonin in the body?

    <p>Enterochromaffin cells of GIT</p> Signup and view all the answers

    Overusage of gadgets at night can lead to a continued increase in ______, preventing melatonin levels from rising.

    <p>serotonin</p> Signup and view all the answers

    Match the following structures with their corresponding hormones or functions:

    <p>Cortex = Adrenaline Medulla = Noradrenaline Pineal gland = Melatonin Enterochromaffin cells = Serotonin</p> Signup and view all the answers

    What is a common consequence of secondary hyperreninemic hyperaldosteronism?

    <p>Hypokalemia</p> Signup and view all the answers

    Diuretics can cause low urine chloride in the late phase.

    <p>True</p> Signup and view all the answers

    List one GI cause and one renal cause of ECF volume contraction.

    <p>GI: Vomiting; Renal: Diuretics</p> Signup and view all the answers

    High urine chloride is typically associated with __________ loss.

    <p>Renal</p> Signup and view all the answers

    Match the following urine chloride levels with their associated conditions:

    <p>Low (&lt; 25 mEq/L) = GI loss or Post-hypercapnia Normal (&gt; 40 mEq/L) = ECF volume expansion High = Renal loss or Diuretics (Early phase)</p> Signup and view all the answers

    What should not be present in the syringe during arterial blood gas analysis?

    <p>Both A and B</p> Signup and view all the answers

    Allen's test is performed to check the patency of the ulnar artery.

    <p>False</p> Signup and view all the answers

    What is the normal range of the anion gap (AG)?

    <p>12 ± 2 mEq/L</p> Signup and view all the answers

    The primary function of the osmolal gap is to determine the presence of unmeasured electrolytes in the blood.

    <p>False</p> Signup and view all the answers

    What is the ideal angle to place the needle during blood sample collection?

    <p>45 degrees</p> Signup and view all the answers

    What is the compensatory HCO₃⁻ limit for chronic respiratory alkalosis?

    <p>12-14 mEq/L</p> Signup and view all the answers

    The wrist should be extended by _____ to _____ degrees during the procedure.

    <p>20, 30</p> Signup and view all the answers

    Match the following parameters with their corresponding changes in values for iced samples at 4°C over 10 minutes:

    <p>pH = 0.001 pCO2 = 0.1 mmHg pO2 = 0.01%</p> Signup and view all the answers

    The formula for calculating the delta ratio is ΔAG divided by Δ _____

    <p>HCO₃⁻</p> Signup and view all the answers

    Match the following components with their corresponding definitions:

    <p>AG = Na⁺ - (HCO₃⁻ + Cl⁻) Osmolal gap = Measured osmolality - Calculated osmolality Corrected AG = AG + 2.5 (4.5 - S.Albumin) Delta Ratio = ΔAG / ΔHCO₃⁻</p> Signup and view all the answers

    What condition is associated with decreased $HCO_3$ levels?

    <p>Metabolic acidosis</p> Signup and view all the answers

    An increase in $HCO_3$ levels will always lead to respiratory alkalosis.

    <p>False</p> Signup and view all the answers

    What change in $PaCO_2$ is expected for every 1 mEq/L decrease in $HCO_3$?

    <p>1.2 mmHg decrease</p> Signup and view all the answers

    For every 1 mEq/L increase in $HCO_3$, the $PaCO_2$ is expected to increase by _____ mmHg.

    <p>0.7</p> Signup and view all the answers

    Match the following acid-base abnormalities with their corresponding primary changes:

    <p>Metabolic Acidosis = ↓ $HCO_3$, ↓ $PaCO_2$ Metabolic Alkalosis = ↑ $HCO_3$, ↑ $PaCO_2$ Respiratory Acidosis = ↑ $PaCO_2$, ↑ $HCO_3$ Respiratory Alkalosis = ↓ $PaCO_2$, ↓ $HCO_3$</p> Signup and view all the answers

    Which type of receptor utilizes G-proteins for downstream signaling?

    <p>G Protein Coupled Receptor</p> Signup and view all the answers

    The alpha subunit of the G protein remains bound to GDP after hormone binding.

    <p>False</p> Signup and view all the answers

    What is the role of cAMP in the GPCR signaling pathway?

    <p>cAMP acts as a second messenger that activates Protein Kinase A (PKA).</p> Signup and view all the answers

    In the inactive state, the G protein is bound to _______.

    <p>GDP</p> Signup and view all the answers

    Match the following hormone receptors with their signaling mechanism:

    <p>G Protein Coupled Receptor = Utilizes G-proteins Tyrosine Kinase Receptor = Utilizes tyrosine kinase activity Janus Kinase/Cytokine Receptor = Utilizes JAK kinases Serine/Threonine Kinase Receptor = Involves serine/threonine kinase activity</p> Signup and view all the answers

    What happens upon activation of the alpha subunit in GPCR signaling?

    <p>It activates the effector molecule.</p> Signup and view all the answers

    The effector molecule is activated during the inactivation stage of the GPCR signaling pathway.

    <p>False</p> Signup and view all the answers

    Name one other possible effector system mentioned in the content that can be triggered.

    <p>Phospholipase C (PLC)</p> Signup and view all the answers

    What is the solubility characteristic of Group I hormones?

    <p>Lipophilic</p> Signup and view all the answers

    Type II receptors are located exclusively in the cytoplasm.

    <p>False</p> Signup and view all the answers

    What is the final cellular response to steroid hormones acting through Type I receptors?

    <p>Activation of gene transcription</p> Signup and view all the answers

    Group II hormones primarily act on the _____ of cells.

    <p>cell membrane</p> Signup and view all the answers

    Match the following hormone groups with their respective characteristics:

    <p>Group I Hormones = Cytoplasm receptors, Lipophilic, Long duration of action Group II Hormones = Cell membrane receptors, Hydrophilic, Short duration of action</p> Signup and view all the answers

    Which of the following hormones is derived from tyrosine?

    <p>Dopamine</p> Signup and view all the answers

    All peptide hormones are larger than 50 amino acids.

    <p>False</p> Signup and view all the answers

    Name one example of a steroid hormone produced in the adrenal cortex.

    <p>Cortisol</p> Signup and view all the answers

    The most abundant adreno-cortical hormone during fetal life is __________.

    <p>DHEAS</p> Signup and view all the answers

    Match the following hormone categories with their examples:

    <p>Amino Acid Derivatives = Adrenaline Peptide Hormones = Oxytocin Steroid Hormones = Estrogen Glycoproteins = TSH</p> Signup and view all the answers

    What activates the Vitamin D Receptor (VDR)?

    <p>Calcitriol</p> Signup and view all the answers

    Vitamin D receptors primarily function in the cytosol.

    <p>False</p> Signup and view all the answers

    What is the primary role of calcitriol in the body?

    <p>Calcium absorption and bone metabolism</p> Signup and view all the answers

    The complex formed by the Vitamin D receptor (VDR) and the retinoid X receptor (RXR) then moves into the ______.

    <p>nucleus</p> Signup and view all the answers

    Which of the following is a dual PPAR agonist?

    <p>Saroglitazar</p> Signup and view all the answers

    Match the following PPAR agonists with their indications:

    <p>Clofibrate = Hypertriglyceridemia Pioglitazone = DM (Combats Insulin Resistance) Saroglitazar = Diabetic dyslipidemia Metformin = Combats Insulin Resistance</p> Signup and view all the answers

    Retinoid X Receptor (RXR) can form heterodimers with Vitamin D Receptors.

    <p>True</p> Signup and view all the answers

    Name one potential side effect of using Pioglitazone.

    <p>Salt &amp; water retention</p> Signup and view all the answers

    Study Notes

    Contraindications for Arterial Blood Gas (ABG) Analysis

    • Abnormal Allen's test indicates compromised blood flow.
    • Infection or anatomical abnormalities at the puncture site increase the risk of complications.
    • Severe peripheral vascular artery disease limits blood flow.
    • Active Raynaud's syndrome makes the vessels susceptible to damage.

    Sites for ABG Puncture

    • Radial artery: Most common site, easily accessible.
    • Femoral artery: Used when radial artery is inaccessible.
    • Brachial artery: May be used, but less common than radial or femoral.
    • Axillary artery: Used sparingly due to deeper location and potential complications.
    • Dorsalis pedis: Used in specific situations.

    Measured Parameters in ABG Analysis

    • pH: Indicates acidity or alkalinity of blood.
    • Partial pressure of carbon dioxide (PCO2PCO_2PCO2​) : Reflects CO2 levels, related to respiratory function.
    • Partial pressure of oxygen (PO2PO_2PO2​) : Indicates oxygen levels, related to respiratory function.
    • Calcium (Ca2+Ca^{2+}Ca2+): Essential for bone health, nerve function, muscle contraction.
    • Chloride (Cl−Cl^-Cl−): Plays a role in fluid balance, electrolyte balance.
    • Creatine Kinase (CK): Enzyme involved in muscle metabolism.
    • Sodium (Na+Na^+Na+): Important electrolyte, influences fluid balance.
    • Glucose: Primary energy source for the body.
    • Hematocrit: Proportion of red blood cells in blood.

    Derived Parameters in ABG Analysis

    • Bicarbonate (HCO3−HCO_3^-HCO3−​): Indicates the amount of bicarbonate in the blood, related to acid-base balance.
    • Anion Gap: Reflects the difference between measured cations and anions, used in diagnosing acid-base disorders.
    • Base Excess: Indicates how much acid or base is needed to bring the blood to normal pH.

    ABG Interpretation: Primary Acid-Base Problems

    • Metabolic Acidosis: Acid buildup in blood, due to inadequate bicarbonate, kidney failure, or diabetic ketoacidosis.
    • Metabolic Alkalosis: Excessive bicarbonate in blood, due to vomiting, diuretic use, etc.
    • Respiratory Acidosis: Buildup of CO2 in blood due to impaired lung function.
    • Respiratory Alkalosis: Loss of CO2 from the body, due to hyperventilation, anxiety, etc.

    ABG Interpretation: Boston Method

    • Normal Values:
      • pH: 7.4
      • PCO2PCO_2PCO2​: 40 mmHg
      • HCO3−HCO_3^-HCO3−​: 24 mEq/L
    • Valid ABG:
      • [H+]=24×PaCO2[H^+] = 24 \times PaCO_2[H+]=24×PaCO2​
      • [HCO3−]=24×PaCO2[HCO_3^-] = 24 \times PaCO_2[HCO3−​]=24×PaCO2​

    Steps in ABG Interpretation Using Boston Method

    • Step 1 - pH:
      • pH < 7.4: Acidosis
      • pH > 7.4: Alkalosis

    Group II Hormones: Principles

    • Mode of Action: Utilize second messengers to influence cellular activity.
    • Mediation: Act via transporter channels, protein synthesis and modification, gene regulation.

    Group II Hormone Receptors

    • G Protein-Coupled Receptors (GPCRs): G-Proteins relay signals inside the cell.
    • Tyrosine Kinase Receptors (TKRs): Utilize tyrosine kinase activity for cellular signaling.
    • Janus Kinase (JAK)/Cytokine Receptors: JAK kinases mediate intracellular signaling.
    • Serine/Threonine Kinase Receptors (STKRs): Serine/threonine kinases initiate intracellular signaling.

    GPCR Mechanism of Action

    • Inactive State: G protein is a complex of alpha, beta, and gamma subunits, bound to GDP. Effector molecule is inactive.
    • Hormone Binding: Hormone binding causes conformational change in receptor, enabling GDP exchange for GTP, activating alpha subunit.
    • Dissociation & Activation: Activated alpha subunit dissociates from the beta-gamma complex, activating the effector molecule.
    • Signal Transduction: Activated effector triggers downstream events, like producing second messengers (e.g., cAMP).
    • Inactivation: GTP hydrolysis to GDP deactivates alpha subunit, which re-associates with beta-gamma dimer. Effector is deactivated, shutting down the pathway.

    Tryptophan Derivatives: Serotonin and Melatonin

    • Sources:

      • Serotonin: Enterochromaffin cells of the gastrointestinal tract.
      • Melatonin: Pineal gland.
    • Function: Involved in the sleep-wake cycle.

      • Serotonin: Promotes wakefulness and alertness.
      • Melatonin: Promotes sleep.

    Mechanism of Serotonin and Melatonin Production

    • Morning: Light signals (Sunlight/gadgets) stimulate ganglion cells of retina, which activate Raphe Nuclei in brainstem, leading to serotonin production.
    • Night (9:30-10 pm): Reduced light signals decrease serotonin levels, leading to increased melatonin production (peaking at 2-2:30 am).

    ECF Volume Contraction: Key Features

    • Secondary hyperreninemic hyperaldosteronism: Elevated renin and aldosterone levels due to ECF contraction, leading to hypokalemia and alkalosis.
    • Reduced Glomerular Filtration Rate (GFR): Leads to lower urine chloride and potassium excretion.
    • Saline-Responsive Alkalosis: Metabolic alkalosis that improves with saline infusion.

    Causes of ECF Volume Contraction

    • Gastrointestinal (GI):
      • Vomiting
      • Nasogastric (NG) aspiration
    • Renal:
      • Diuretic use
      • Post-hypercapnia (respiratory acidosis)
      • Cystic fibrosis

    Urine Chloride Interpretation

    • Low (< 25 mEq/L): Suggests GI loss, post-hypercapnia, cystic fibrosis, or diuretic use (late phase).
    • Normal (> 40 mEq/L): Indicates ECF volume expansion.
    • High (urine chloride): Suggests renal loss, diuretic use (early phase), Bartter syndrome, or Gitelman syndrome.

    Acid Generation in ECF Volume Contraction

    • High Anion Gap: Indicates metabolic acidosis caused by acid buildup.

    Alkali Loss in ECF Volume Contraction

    • Gastrointestinal Causes:
      • Non-anion gap metabolic alkalosis (NAGMA) (-ve), due to loss of H+ ions.
      • VIPoma (tumor secreting vasoactive intestinal peptide- VIP).
    • Renal Causes:
      • NAGMA (+ve), due to renal H+ retention.
      • Renal tubular acidosis (RTA).

    ABG Analysis Methods

    • Boston: Commonly used, assumes normal values to calculate derived parameters.
    • Copenhagen: Accounts for individual variability in values.
    • Stewarts: Emphasizes the roles of strong ions and weak acids in acid-base balance.

    ABG Analysis: Compensatory Limits

    • Respiratory Acidosis:
      • Acute: HCO3- levels increase.
      • Chronic: HCO3- levels increase up to 45 mEq/L.
    • Respiratory Alkalosis:
      • Acute: HCO3- levels decrease.
      • Chronic: HCO3- levels decrease up to 12-14 mEq/L.

    Anion Gap

    • Definition: Difference between measured cations and anions, reflecting unmeasured anions.
    • Formula: Na⁺ - (HCO₃⁻ + Cl⁻)
    • Normal Value: 12 ± 2 mEq/L
    • Corrected Anion Gap: AG + 2.5 (4.5 - S.Albumin)

    Osmolal Gap

    • Definition: Difference between measured and calculated osmolality.
    • Calculation: 2(Na⁺) + BUN + Glucose + 1.25 x EtOH (in mmol/L)
    • Normal Value: Close to zero.
    • Increased Gap: Suggests presence of unmeasured osmotically active molecules (e.g., methanol, ethylene glycol).

    Delta Ratio

    • Delta AG: Difference between measured and normal anion gap.
    • Formula: Delta AG / ΔHCO₃⁻
    • Interpretation: 2: Indicates high anion gap metabolic acidosis (HAGMA) with metabolic alkalosis.

    ABG Analysis: Methodology

    • Equipment:
      • ABG analyzer
      • 1 ml syringe with needle (0.5 ml heparinized): Important to use the right heparin amount.
      • 70% alcohol wipe, gauze, gloves
    • Procedure:
      • Palpate radial artery.
      • Occlude ulnar artery.
      • Perform Allen's test for radial artery patency.
      • Needle at 45 degrees.
      • Wrist extension (20-30 degrees).
      • Sterilize area.
      • Collect blood sample.
      • Cap the needle, transport promptly.

    ABG Analysis: Pre-requisites

    • Syringe should contain more than 50% blood.
    • Volume of the syringe should be 3 ml or less.
    • No air bubbles (↑pOA, ↑pCOA).
    • Ensure cold chain maintenance.

    ABG Analysis: Precautions

    • Flush syringe with 0.5 ml of 1:1000 heparin solution, then empty it.
    • Excess heparin leads to dilutional effects.
    • Transport the sample immediately via cold chain.
    • Delays can alter values.

    ABG Analysis: Value Changes over Time

    • Cold Sample (4°C):
      • pH: 0.001 change per 10 minutes.
      • pCO₂: 0.1 mmHg change per 10 minutes.
      • pO₂: 0.01% change per 10 minutes.
    • Uniced Sample (37°C):
      • pH: 0.01 change per 10 minutes.
      • pCO₂: 1 mmHg change per 10 minutes.
      • pO₂: 0.1% change per 10 minutes.

    Acid-Base Imbalance Diagnosis: Flowchart Approach

    • Step 1: pH: Determines whether acidosis or alkalosis exists.
    • Step 2: Primary Metabolic Abnormality: Determined by changes in HCO3- and PaCO2.
    • Step 3: Compensatory Changes: Analyze the body's response to the primary abnormality.

    Acid-Base Imbalance: Primary Metabolic Abnormality

    • Decreased HCO3-: Indicates metabolic acidosis.
    • Increased HCO3-: Indicates metabolic alkalosis.

    Acid-Base Imbalance: Compensatory Changes

    • Metabolic Acidosis: Compensated via respiratory alkalosis.
    • Metabolic Alkalosis: Compensated via respiratory acidosis.

    Acid-Base Imbalance Changes in HCO3- and PaCO2

    • Every 1 mEq/L decrease in HCO3-: Corresponds to a 1.2 mmHg decrease in PaCO2.
    • Every 1 mEq/L increase in HCO3-: Corresponds to a 0.7 mmHg increase in PaCO2.

    Acid-Base Imbalance: Respiratory Abnormality

    • Respiratory Acidosis: Increased PaCO2 and HCO3- levels.
    • Respiratory Alkalosis: Decreased PaCO2 and HCO3- levels.

    Acid-Base Imbalance: Adequacy of Compensation

    • Adequate Compensation: Values fall within the expected range.
    • Partial Compensation: Values fall between the expected and normal ranges.

    Hormone Mechanism of Action: Classification

    • Group I Hormones: Intracellular, lipophilic, long duration of action.
    • Group II Hormones: Cell membrane receptors, hydrophilic, short duration of action.

    Hormone Receptors: Type I (Homodimers)

    • Location: Cytoplasm.
    • Hormones: Steroid hormones (e.g., testosterone).

    Hormone Receptors: Type II (Heterodimers)

    • Location: Not specified (implied to be related to the nucleus).
    • Hormones: Thyroid hormones (T3/T4), Vitamin A derivatives, others.

    Type I Receptors: Mechanism of Action (Steroid Hormones)

    • Entry: Steroid hormones enter the cytoplasm.
    • Receptor Binding: They bind to inactive receptors (bound to Hsp-90).
    • Activation: Binding causes dissociation of Hsp-90, forming the R-4 complex (active).
    • Nuclear Translocation: The complex moves to the nucleus.
    • DNA Binding: Complex binds to glucocorticoid response elements (GREs).
    • Gene Transcription: This binding activates gene expression, leading to protein synthesis.
    • Cellular Response: The hormone ultimately triggers a response in the cell.

    Overview of Hormones: Vitamin D Receptor (Type II)

    • Calcitriol: Active form of vitamin D.
    • VDR: Vitamin D receptor.
    • RXR: Retinoid X Receptor.
    • Heterodimer Formation: Calcitriol activates VDR, which binds to RXR, forming a heterodimer.
    • Nuclear Translocation: This complex enters the nucleus.
    • Gene Transcription: Binds to target genes, triggering gene expression.

    Vitamin D Receptor Signaling

    • HSP: Heat Shock Protein.
    • VDR: Vitamin D Receptor.
    • RXR: Retinoid X Receptor.
    • VDRE: Vitamin D Response Elements.

    Nuclear Receptor Signaling: General Principles

    • Homodimers or Heterodimers: Receptors can form dimers with themselves or other receptors.
    • Ligand-Induced Activation: Binding of a ligand to a receptor triggers downstream signaling.

    PPAR Agonists: Types and Effects

    • PPAR Alpha Agonist: Clofibrate, used to lower hypertriglyceridemia.
    • PPAR Gamma Agonist: Pioglitazone, used for diabetes (combats insulin resistance), but has potential side-effects (water retention, fractures, bladder cancer).
    • Dual PPAR Alpha & Gamma Agonist: Saroglitazar, used for diabetic dyslipidemia, NAFLD (Non Alcoholic Fatty Liver Disease), and NASH (Non Alcoholic Steatohepatitis).

    Hormone Classification: Based on Structure

    • Amino Acid Derivatives:

      • Tyrosine Derivatives:
        • T3 (triiodothyronine): Thyroid hormone.
        • T4 (thyroxine): Thyroid hormone.
        • Catecholamines (Adrenal medulla):
          • Adrenaline: Main catecholamine.
          • Noradrenaline.
          • Dopamine.
      • Tryptophan Derivatives:
        • Serotonin: Neurotransmitter and hormone.
        • Melatonin.
      • Vitamin Derivatives:
        • Vitamin A.
        • Vitamin D.
    • Peptide Hormones:

      • Small Peptides (< 50 amino acids):
        • ACTH: Adrenocorticotropic hormone.
        • ADH (vasopressin): Antidiuretic hormone.
        • Oxytocin: Hormone involved in bonding and childbirth.
        • All hypothalamic hormones: Regulate pituitary function.
        • Growth Hormone: Plays a role in growth and development.
        • Prolactin: Hormone related to milk production.
        • Insulin: Hormone regulates blood glucose levels.
      • Large Peptides (> 50 amino acids):
        • PTH: Parathyroid hormone regulates calcium levels.
        • Renin: Enzyme involved in blood pressure regulation.
        • FSH: Follicle-stimulating hormone involved in reproduction.
        • LH: Luteinizing hormone involved in reproduction.
        • TSH: Thyroid-stimulating hormone regulates thyroid function.
    • Glycoproteins (Protein > carbohydrate):

      • Aldosterone: Produced in adrenal zona glomerulosa, regulates electrolytes.
      • Cortisol: Produced in adrenal zona fasiculata, regulates stress response.
      • Adrenal androgens/Sex steroids (zona reticularis):
        • DHEAS (Dihydroepiandrosteronesulfate): The most abundant adreno-cortical hormone in fetal life.
        • Androstenedione.
    • Steroid Hormones:

      • Adrenal Cortex Hormones:
        • Aldosterone.
        • Cortisol.
        • Adrenal androgens,
      • Sex Steroids:
        • Estrogen.
        • Progesterone.
        • Testosterone.

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    Test your knowledge on key concepts from Physiology Chapter 5. This quiz covers arterial blood gas analysis, acid-base disorders, and hormonal functions related to sleep. See how well you understand these important physiological mechanisms!

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